The over-arching objectives of the Neuromedical Core (NMC) are to provide comprehensive clinical and[unreadable] laboratory evaluations, scientific consultation, and mentorship, training, and community education in[unreadable] NeuroAIDS. In the current funding period the NMC facilitated 79 research projects including observational[unreadable] cohort studies, clinical-pathological investigations, imaging studies, clinical trials and international research[unreadable] performed by collaborating investigators at UCSD and many other institutions. The HNRC's collaborating[unreadable] investigators find data generated by the NMC, including neurological diagnostic formulations, antiretroviral[unreadable] (ARV) treatment information, HIV disease staging information, viral loads and a variety of other clinical[unreadable] laboratory measurements, to be essential for their data analyses and publications.[unreadable] Recognizing that maintaining vitality and scientific relevance necessitates continual adaptation to the[unreadable] changing needs of the HNRC research enterprise and the scientific agendas of its many principal[unreadable] investigators and collaborators, we propose to enhance the NMC in this renewal in two ways. First, we will[unreadable] add a pharmacology component that will focus on ARV drug penetration into the CMS. Second, we will[unreadable] incorporate functions previously carried out by the Cellular Immunology and Fluids Core. The newly-organized[unreadable] NMC is made up of three cooperative units, each comprising common resources (equipment,[unreadable] supplies) and staff that interact on a daily basis: a Clinical Unit; a Patient-Derived Sample Unit; and a[unreadable] Pharmacology & Biomarker Unit. Examples of scientific questions the Core will facilitate answering are[unreadable] 1) What is the contributory role in neuroAIDS of co-pathogens and comorbidities such as hepatitis C virus[unreadable] (HCV) and substance abuse? 2) Does cerebrospinal fluid (CSF) provide a useful window to evaluate[unreadable] virus-host interactions and molecular pathogenesis in neuroAIDS? 3) What is the role of the CNS in viral[unreadable] evolution, adaptation and the occurrence of ARV drug resistance? 4) How do host genetics influence HIV[unreadable] neuropathogenesis?[unreadable] By assisting investigators in widely diverging disciplines at all levels of project development, from[unreadable] conceptualization of hypotheses to study implementation, analysis, interpretation and dissemination, the[unreadable] NMC encourages the application of multiple scientific perspectives and stimulates interdisciplinary[unreadable] collaboration and coordination. We will collaborate closely with the Neuroimaging, Neurobehavioral,[unreadable] Neurovirology and Neurobiology Cores to further stimulate transdisciplinary aims. In addition to supporting[unreadable] the performance of research research, the NMC also enhances and extends the effectiveness and public[unreadable] health impact of new findings related to mental health and HIV/AIDS.[unreadable]